This research is based on the hypothesis that an altered metabolism by the brain of oxidative reaction products, such as superoxide radical and hydrogen peroxide, may be of fundamental importance in the pathogenesis of Alzheimer's disease. Three enzymes are primarily involved in protection against these oxidative reaction products: superoxide dismutase, catalase and glutathione peroxidase. Biochemical studies have shown that the first enzyme is plentiful in brain, but the content of the other two is low. In this project, pilot studies will test new techniques and develop, or explore the feasibility of devising, suitable methods for demonstrating the presence and localization of these three enzymes in animal (rat, mouse, guinea pig and/or rabbit) and human brain. Histochemical procedures utilizing cerium and diaminobenzidine are expected to be useful for animal and possibly human tissue. Where antisera are available, immunocytochemical methods with horseradish peroxidase may be advantageous for human brain. The pilot studies in this project will permit subsequent investigations with animal and human brain on the presence and localization of the three enzymes in different species and in various brain regions and cell types. The enzymes can then be examined during normal development and aging and in Alzheimer's disease, with a focus on central cholinergic neurons, which are particularly affected in this condition. Such a study may indicate the usefulness of the hypothesis that altered metabolism of oxidative reaction products plays a role in the pathogenesis of Alzheimer's disease.